Although this invention has a variety of both optical and non-optical applications as described below, it is especially suitable for treating post-operative glaucoma patients. Because the use of this invention in treating post-operative glaucoma patients is representative of the other possible applications of this invention, this preferred embodiment will be described below in greater detail.
Glaucoma is a major cause of irreversible blindness in the United States. The National Advisory Eye Council estimated in 1978 that 62,000 Americans were blind as the result of glaucoma. Glaucomatous visual loss is usually associated with elevated intraocular pressures which damage the optic nerve. Glaucoma treatment is therefore directed toward lowering the intraocular pressure. In most glaucoma patients medical therapy (topical eye drops and oral tablets) adequately lowers intraocular pressure. When these measures are inadequate, laser therapy is often performed. If laser therapy is also unsuccessful, glaucoma surgery is required. Glaucoma filtration surgery is the most common type of glaucoma surgery. The purpose of this type of operation is to make an opening between the anterior chamber of the eye and the subconjunctival space to allow for the drainage of aqueous humor from the eye. This results in lowering the intraocular pressure. Failure of filtration surgery is usually attributed to the proliferation of fibroblasts and scarring at the filtering site. As a consequence of this scarring, the drainage canal opened by surgery is gradually obstructed by scar tissue and eventually sealed thereby necessitating further surgery.
Eyes undergoing glaucoma filtration surgery have a seventy-five percent to ninety percent chance of achieving intraocular pressure control following a first filtering procedure. The success rate of filtering surgery in eyes that have had unsuccessful previous filtering surgery is generally less than after the initial filtering procedure. Aphakic patients who undergo filtering surgery are also less likely to achieve adequate intraocular pressure control than phakic patients. The surgical prognosis for filtration operations are also less favorable for neovascular glaucoma and in young patients.
Various techniques have been tried to improve the success rate of glaucoma filtration surgery. These include the application of a variety of drugs that inhibit or prevent scarring and fibroblastic proliferation at the drainage site such as steroids and antimetabolites such as 5-fluorouracil. Artificial drainage implants of different designs have also been used in an attempt to form a permanent drainage tract into the extraocular tissues. For example, U.S. Pat. Nos. 3,788,327 (Donowitz et al.) and 4,402,681 (Haas et al.) disclose non-erodible ocular implants which consist of a body portion and a stem/valve portion designed for the purpose of maintaining an open, drainage canal following glaucoma surgery to relieve intraocular pressure.
All of these prior art methods and devices, however, have their own particular limitations and complications. For drug treatment, there is the difficulty of regularly or continuously administering a controlled dose of the drug to a localized site over a prolonged period of time. The use of a non-erodible ocular implant may require subsequent surgery to remove the device. Often, scar tissue can proliferate and occlude the nonerodible ocular implant. The nonerodible ocular implant composed of a substance foreign to the body may be extruded over time or become a site of infection or inflammation.
One recent approach to these problems has involved the use of bioerodible polymer/drug combinations in a variety of ways to achieve a controlled regular or continuous administration of the drug. Bioerodible polymers are useful as carriers for many different types of drugs because they serve as a temporary matrix to hold the drug, but do not chemically interact with the drug. As the matrix erodes, the drugs are released and can diffuse into the tissues.
In one embodiment, the bioerodible polymer matrix is homogeneously impregnated with the drug so that the drug is released more or less continuously and uniformly as the supporting polymer matrix erodes. In another variation of this basic idea, a single reservoir of the drug in liquid or solution form is encapsulated by a semi-porous polymer matrix. The drug diffuses continuously out of the reservoir, through the polymer, and finally to the intended delivery area. In still a further variation, tiny discrete "pockets" of the drug are encapsulated throughout the polymer. If the polymer is bioerodible, eventually it will completely dissolve thereby releasing all of the impregnated or encapsulated drug.
For example, U.S. Pat. Nos. 3,993,071 (Higuchi et al.); 3,986,510 (Higuchi et al.); 3,981,303 (Higuchi et al.); and, 3,960,150 (Hussain et al.) broadly disclose the concept of bioerodible ocular inserts designed for continuous, controlled administration of a medication to the eye. These patents comprehensively disclose a wide array of the following features:
(a) ocular problems which can benefit from the use of the subject inserts, specifically including treatment of glaucoma;
(b) useful drug/bioerodible matrix combinations, specifically including the group of miotics and anticholinesterases such as pilocarpine;
(c) useful insert shapes including ellipsoid, donut-shape, bean-shape, banana-shape, circular, and rectangular; and,
(d) drug release control techniques ranging from a more or less homogeneous bioerodible matrix with medication dispersed throughout to a single drug reservoir inside the support matrix including one embodiment employing microencapsulation of the drug within the support matrix.
Other recent patents which disclose various types and shapes of bioerodible ocular inserts include U.S. Pat. Nos. 3,995,635 (Higuchi et al.) 4,142,526 (Zaffroni et al.); 3,963,025 (Whitaker et al.); 4,484,922 (Rosenwald); 4,439,198 (Brightman); 3,811,444 (Heller et al.); 3,867,519 (Michaels); and 3,962,414 (Michaels).
U.S. Pat. Nos. 4,190,642 (Gale et al.); 4,179,497 (Cohen et al.); and 3,911,098 (Capozza) show various drug/matrix combinations especially intended for treating eye problems. Gale et al. discloses a non-erodible ocular insert intended specifically for managing intraocular pressure, and Cohen et al. discloses an erodible insert for the same purpose. All of the above-cited prior art is hereby specifically incorporated herein by reference.
As is evident from a review of the above patents, the area of bioerodible eye inserts which serve as controlled-rate drug delivery vehicles is a very crowded field. None of the above-cited patents, however, discloses a bioerodible ocular implant capable of controlled-rate drug delivery to a specific localized intraocular site nor one which is designed to function so as to maintain a drainage canal utilizing both therapeutic and mechanical means. As used in this application, the term "implant" is intended to specifically distinguish the bioerodible devices of this invention, which are designed for internal surgical placement, from the "inserts" of the prior art which are employed externally or in areas accessible without surgery such as at the surface of the conjunctival membrane in the eye.
All of the bioerodible inserts disclosed by the prior art are designed and specifically intended for extraocular use. They are typically positioned on the surface of the conjunctival membrane between the upper or lower lids of the eye and the sclera or outer surface of the eyeball (e.g. FIGS. 1 and 2, described at col. 5, 11. 11-44, of U.S. Pat. No. 3,993,071). As a result, as the polymer matrix erodes, medication is delivered to the entire conjunctival area and across the entire surface of the cornea. Such generalized delivery of the medication may restrict the type or concentration of medication that can be employed. Furthermore, because the inserts of these prior art patents are applied to the surface of the eyeball, at best only a small fraction of the medication can reach intraocular sites where the medication may really be needed. Even to the extent that some of the medication may penetrate to intraocular sites, the devices and methods of the prior art patents in this area serve only as vehicles for holding and gradually releasing the medication. The structural elements of these devices serve no beneficial mechanical functions.